Chronic ethanol consumption impairs receptor-mediated endocytosis of MAA-modified albumin by liver endothelial cells

Michael J. Duryee, Lynell W. Klassen, Thomas L. Freeman, Monte Willis, Dean J. Tuma, Geoffrey M. Thiele

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Alcoholic liver disease has been associated with abnormalities in receptor-mediated endocytosis (RME) which results in abnormal degradation of metabolically altered proteins. Model systems using formaldehyde-modified albumin (f-Alb) have shown an impairment in RME following chronic alcohol consumption utilizing both in situ perfused rat livers and isolated rat liver endothelial cells (LECs). The discovery that alcohol metabolite derived aldehydes can modify proteins prompted a study to determine if malondialdehyde-acetaldehyde-modified albumin (MAA-Alb) would be degraded similar to that reported for f-Alb, and whether ethanol-fed rats would demonstrate an impaired RME with respect to this ligand which occurs as a consequence of chronic ethanol consumption. MAA-Alb was degraded slightly more than f-Alb in both in situ perfused livers and at the single cell level. This degradation was completely inhibited with 100× unlabeled f-Alb, which suggests the use of a similar receptor. Following alcohol consumption there was a 50-60% decrease in MAA-Alb degradation in whole livers and isolated LECs. Utilizing isolated LECs it was determined that impairment in internalization was the most likely mechanism for the decrease in the amount of MAA-Alb that was degraded. These data show that chronic alcohol consumption by rats does in fact impair RME of alcohol metabolite-derived adducted proteins, and this impairment is due to a defect in the post-internalization step rather than the binding or degradation of the modified protein.

Original languageEnglish (US)
Pages (from-to)1045-1054
Number of pages10
JournalBiochemical Pharmacology
Volume66
Issue number6
DOIs
StatePublished - Sep 15 2003
Externally publishedYes

Fingerprint

Endothelial cells
Endocytosis
Liver
Albumins
Ethanol
Endothelial Cells
Acetaldehyde
Malondialdehyde
Formaldehyde
Alcohols
Rats
Alcohol Drinking
Degradation
Metabolites
Proteins
Alcoholic Liver Diseases
Aldehydes
Proteolysis
Ligands
Defects

Keywords

  • Alcohol
  • Aldehyde-modified proteins
  • Liver endothelial cells
  • Protein degradation
  • Receptor-mediated endocytosis
  • Scavenger receptors

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

Cite this

Chronic ethanol consumption impairs receptor-mediated endocytosis of MAA-modified albumin by liver endothelial cells. / Duryee, Michael J.; Klassen, Lynell W.; Freeman, Thomas L.; Willis, Monte; Tuma, Dean J.; Thiele, Geoffrey M.

In: Biochemical Pharmacology, Vol. 66, No. 6, 15.09.2003, p. 1045-1054.

Research output: Contribution to journalArticle

Duryee, Michael J. ; Klassen, Lynell W. ; Freeman, Thomas L. ; Willis, Monte ; Tuma, Dean J. ; Thiele, Geoffrey M. / Chronic ethanol consumption impairs receptor-mediated endocytosis of MAA-modified albumin by liver endothelial cells. In: Biochemical Pharmacology. 2003 ; Vol. 66, No. 6. pp. 1045-1054.
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